Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vasoactive peptides contain a high proportion of proline residues which make them resistant to hydrolysis by many peptidases. However, post proline cleaving enzyme (PPCE; EC 3.4.21.26), a proline specific endopeptidase which specifically hydrolyzes internal peptide bonds on the carboxyl side of proline residues, has been shown to inactivate numerous vasoactive peptides including angiotensins, kinins, substance P, vasopressin and oxytocin. In order to determine whether PPCE could be involved in vascular metabolism of vasoactive peptides, we carried out localization and characterization studies of PPCE-like activity in hog aorta and mesenteric artery. PPCE was assayed fluorometrically at pH 7.0 using the specific PPCE substrate CBZ-Gly-Pro-4-methyl-coumarinylamide. The subcellular distribution of vascular PPCE was essentially the same as that of the cytosolic marker enzyme lactic dehydrogenase (LDH). PPCE was enriched six-fold in the cytosolic fraction (11.4 +/- 2.7 units/mg) and unlike the plasma membrane-bound proline specific exopeptidase dipeptidyl-(amino)peptidase IV (DAP IV; EC 3.4.14.5), little or no activity could be detected in the microsomal or plasma membrane fractions. Similar to PPCE characterized from other sites, vascular PPCE was stabilized and activated by dithiothreitol and EDTA, and inhibited by DFP, p-chloromercuriphenyl sulfonic acid, L-1-tosylamido-2-phenylethylchloromethyl ketone, Cu++, Ca++, and Zn++. Vascular PPCE was unaffected by inhibitors of trypsin and kallikrein (Aprotinin, ABTI), aminopeptidase M (bestatin, amastatin), neutral endopeptidase (phosphoramidon), angiotensin I converting enzyme (captopril) or carboxypeptidase N (MERGETPA). These data demonstrate that PPCE is present in vascular endothelium and/or smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Vascular, post proline cleaving enzyme: metabolism of vasoactive peptides. 354 18

The subcellular distribution of prolyl endopeptidase, and of cation-sensitive neutral endopeptidase, two enzymes actively metabolizing many neuropeptides, was determined in homogenates of rabbit brain. The subcellular distribution of both enzymes was more similar to lactate dehydrogenase, a cytoplasmic enzyme marker, than to choline acetyltransferase, a synaptosomal marker. Only 35% of the activity of these two neutral endopeptidases was found in the crude mitochondrial fraction (P2), the bulk of the remaining activity being associated with the high-speed supernatant. Prolyl endopeptidase and cation-sensitive neutral endopeptidase thus can be regarded as mainly cytoplasmic enzymes in the rabbit brain.
 ...
PMID:Subcellular distribution of prolyl endopeptidase and cation-sensitive neutral endopeptidase in rabbit brain. 703 48

The CD34 antigen was detected on > or = 10% of the blast cells in 235 (70%) of 335 cases of newly diagnosed childhood acute lymphoblastic leukemia (ALL) treated in two consecutive chemotherapy trials. By immunophenotype, the distribution of positive cases favored early pre-B ALL (83%; n = 180) followed by pre-B ALL (61%; n = 89) and then T-cell ALL (46%; n = 61) (P < .001). Among the B-lineage cases, CD34 expression was significantly associated with favorable presenting features: age 1 to 10 years, white race, absence of central nervous system (CNS) leukemia, low serum lactate dehydrogenase level, CD10 expression, and leukemic cell hyperdiploidy (> 50 chromosomes or DNA index > or = 1.16). Event-free survival was clearly superior for patients with CD34+ leukemia (P = .01), with an estimated 83% +/- 6% (SE) of the cohort remaining free of adverse events at 5 years post diagnosis, as compared to 63% +/- 10% of the group without this feature. Multivariate analysis showed that the prognostic influence of the antigen was independent of age, leukocyte count, and other well-recognized factors, suggesting that it would add discriminatory power to current systems of risk assignment. Findings in T-cell ALL were the reverse: CD34 expression showed positive correlations with initial CNS leukemia and CD10 negativity but not with any good-risk presenting characteristics. Log-rank analysis indicated no adverse effect on treatment outcome by CD34 antigen expression, although additional patients with need to be studied to obtain a definitive answer. The opposed clinical associations of CD34 expression in B- and T-lineage ALL may reflect fundamental biologic differences between these leukemia species.
 ...
PMID:Clinical significance of CD34 expression in childhood acute lymphoblastic leukemia. 768 97

gamma-Glutamyl hydrolase is a ubiquitous enzyme that has the capacity to cleave gamma-glutamyl bonds of cellular folyl- and antifolylpoly-gamma-glutamates. This study has revealed that the enzyme is secreted by primary cultures of rat hepatocytes and by H35 hepatoma cells. It was found that more than 99% of the total enzyme from H35 cells accumulated in the medium after 48 hr incubation with the serum-free medium. The cells were shown to remain intact during the secretion period since lactate dehydrogenase, dihydrofolate reductase and lysosomal hydrolases other than gamma-glutamyl hydrolase were retained within the cell. When PteGlu5 (folylGlu4) is used as a substrate the initial product is PteGlu (folate), and there is no appearance of intermediate chain length pteroyl polyglutamates. Therefore, the secreted and cellular gamma-glutamyl hydrolase from hepatoma cells appears to be an endopeptidase. Polyclonal antibodies to the poly-gamma-glutamate substrates of the enzyme were prepared and characterized. The antibodies recognize the structural differences between alpha- and gamma-glutamyl linkages but appear equally active with PteGlu5 and its analogs such as 4-NH2-10-CH3PteGlu5 and pABAGlu5. The affinity of the antibodies is related to the gamma-glutamyl structure since L-glutamic acid, folate or p-aminobenzoic acid are inactive with the antibodies. Furthermore, poly-gamma-glutamate has lower affinity for the antibodies than the poly-gamma-glutamate derivatives of PteGlu, 4-NH2-10-CH3PteGlu or pABA.
 ...
PMID:The properties and function of gamma-glutamyl hydrolase and poly-gamma-glutamate. 768 89

Eleven cases of cutaneous B-cell lymphoma (CBCL) were studied. The ages at presentation ranged from 34 to 79 years (mean = 59.9 years). Six patients were female and five male. Five of the 11 patients had a solitary tumour and the other six had multiple tumours at initial presentation. According to Burg's classification, six cases were at stage I, two stage II, two stage III and one was at stage IV at initial presentation. Abnormalities in laboratory data were rare, except for serum lactic dehydrogenase values. Epidermotropism was not detected, and the area mainly affected by neoplastic cells was the reticular dermis (seven cases) and subcutis (four cases). Biopsy specimens from the patients analysed by immunohistochemical techniques on paraffin or cryostat sections showed CD20 and/or CD22 positivity. Biopsy specimens from two patients which showed CD10 positivity were diffuse large cell types by the working formulation and presented as pre-B-cell lymphoma. At least two groups of CBCL were demonstrable on the basis of prognosis. One was a benign low-grade lymphoma presenting with solitary tumours, mature B-cell markers and intermediate-grade pathology, and the other was a high-grade lymphoma with multiple tumours, pre-B-cell or mature B-cell markers and a poor prognosis.
 ...
PMID:Cutaneous B-cell lymphoma--a clinical, pathological and immunohistochemical study. 825 90

In vivo, bicarbonate can affect proximal tubule intermediary metabolism, including gluconeogenesis, ammoniagenesis and maintenance of the mitochondrial substrate supply. In vitro, rabbit proximal tubule cells (RPTC) in primary culture revert from gluconeogenesis to glycolysis and their mitochondrial metabolism remains lower than in vivo. To determine whether the bicarbonate buffer system could have an effect on these deregulations, RPTC in primary culture grown in the absence of insulin and glucose in the culture medium were developed either with the standard sodium bicarbonate buffer with 5% CO2 or with a Hepes hydrogen ion buffer in the presence of 0.5% CO2. Duration of the bicarbonate-free cultures was increased until at least day 17 after seeding, compared with day 11 in bicarbonate-buffered cultures. As could be expected, succinate dehydrogenase activity remained stable as a function of time in bicarbonate-free cultures while an early marked decrease of this activity occurred from seeding in cultures developed in the presence of bicarbonate buffer. Compared to bicarbonate-buffered cells, higher phosphoenolpyruvate carboxykinase activity concomitant with lower intracellular lactate dehydrogenase activity was observed in cultures developed in the absence of bicarbonate, which is indicative of closer carbohydrate metabolism orientation to the in vivo situation for RPTC. Immunofluorescence staining of RPTC with monoclonal antibodies directed to neutral endopeptidase (NEP), and dipeptidyl-peptidase IV (DPP II) showed similar extensive labelling with DPP and NEP in both culture conditions. Confocal microscopy analysis of NEP subcellular distribution, showed exclusive targetting of NEP to the apical plasma membranes. In both models, cAMP production was stimulated by parathyroid hormone and unaffected by arginine vasopressin. In conclusion, bicarbonate withdrawal from the culture medium (without changing the pH of the medium) allows a marked improvement of mitochondrial capacity and carbohydrate metabolism pattern without any loss of differentiated properties.
 ...
PMID:Effects of the medium HCO3-/CO2 buffer system on differentiation and intermediary metabolism properties of rabbit proximal tubule cells in primary culture. 897 88

We report on a series of 26 patients diagnosed with primary (de novo) plasma cell (PC) leukemia (PCL) in whom we analyzed the clinicobiologic characteristics of the disease together with the immunophenotype, DNA cell content, proliferative index, and numeric chromosomal aberrations of the neoplastic PC, and compared them with 664 multiple myeloma (MM) patients at diagnosis. The median age, sex ratio, and bone lesion extension were similar, but PCL cases displayed a higher prevalence of clinical stage III, extramedullary involvement, and Bence Jones cases, with fewer IgA cases than for MM patients. In addition, according to several prognostic indicators (beta2-microglobulin serum level, proportion of S-phase PCs, proteinuria, calcium serum level, lactate dehydrogenase [LDH] and renal function), the incidence of adverse prognostic factors was significantly higher in PCL versus MM. Immunophenotypic expression was similar for CD38, CD138, CD2, CD3, CD16, CD10, CD13, and CD15, but PCL differed from MM in the expression of CD56, CD9 HLA-DR, CD117, and CD20 antigens. Twenty-two PCL cases were diploid and one was hypodiploid, while most MM cases (57%) showed DNA hyperdiploidy. With the fluorescent in situ hydridization (FISH) technique, 12 of 13 PCL cases displayed the numeric aberrations, -13 (86%), +/-1 (57%), +18 (43%), and -X in women (25%), but they lacked several numeric aberrations usually found in MM such as +3, +6, +9, +11, and +15. PCL cases had a lower overall response to therapy than MM cases (38% v 63%, P =.01332). Among PCL patients, a trend for a worse response was observed in cases treated with melphalan and prednisone (MP) versus polychemotherapy. Overall survival was significantly worse in PCL versus MM patients (8 v 36 months, P <.0001), but it was significantly better in PCL patients treated with polychemotherapy versus MP (18 v 3 months, P =.0137). By contrast, MM patients did not show significant differences in overall survival according to the treatment used, MP or polychemotherapy. Ten variables seemed to predict survival in PCL patients, but only the beta2-microglobulin level and S-phase PCs retained an independent value in multivariate analysis. In summary, our study illustrates that PCs from PCL display singular phenotypic, DNA cell content, and cytogenetic characteristics that lead to a different disease evolution versus MM.
 ...
PMID:Primary plasma cell leukemia: clinical, immunophenotypic, DNA ploidy, and cytogenetic characteristics. 1061 Jan 15

Seven patients with peripheral B-cell lymphoma associated with hemophagocytic syndrome are reported. In all cases, the histologic subtype was diffuse large B-cell lymphoma. Hemophagocytic features were noted in the bone marrow with lymphomatous infiltration. Hemophagocytic syndrome occurred with presentation of the lymphoma and was characterized by high fever, cytopenias, and elevated levels of lactate dehydrogenase, ferritin, C-reactive protein, and cytokines [interferon gamma, macrophage colony-stimulating factor, soluble interleukin (sIL)-2R, and IL-6] without evidence of infection. The phenotypes of lymphomas were suspected CD19+, CD20+, S-Ig+, CD10-, and coexpression of CD5 in some cases. Flow cytometric analysis showed a low CD4/CD8 ratio in peripheral blood and bone marrow. We suggest that the pathogenesis of hemophagocytic syndrome is hypercytokinemia induced by a proliferation of reactive CD8+ T cells. Previous reports of B-cell lymphoma with hemophagocytic syndrome demonstrated similar clinical manifestations and poor prognoses. The invasion patterns of these diffuse large B-cell lymphomas with hemophagocytosis may be classified into three groups: microscopic lymph-node involvement type, gross lymph-node involvement type, and splenic lymphoma type. Although hemophagocytic syndromes have been reported to be associated with T-cell lymphomas, our results indicate an association with diffuse large B-cell lymphoma.
 ...
PMID:B-cell lymphoma-associated hemophagocytic syndrome: clinicopathological characteristics. 1096 86

The clinical significance and prognostic value of CD10 in de novo diffuse large B-cell lymphoma (DLBCL) is largely unknown. We retrospectively studied 19 men and 9 women based on the following criteria: (1) DLBCL with no evidence of concomitant or antecedent follicular lymphoma; (2) available flow cytometric immunophenotyping data, including CD10 status; (3) older than 15 years; (4) specific exclusion of high-grade, Burkitt-like lymphoma; and (5) exclusion of primary cutaneous DLBCL. When available, clinical data at diagnosis, including components of the international prognostic index, were reviewed. Eleven cases were CD10+, and 17 were CD10-. There was no significant difference between the CD10+ and CD10- groups in age, sex, stage, performance status, extranodal involvement, or serum lactate dehydrogenase levels at diagnosis. However, in the 26 cases for which follow-up data were available, the CD10+ group displayed a shorter overall survival than the CD10- group (8 vs 30 months). Although the clinical findings at diagnosis are similar in CD10+ and CD10- DLBCL, CD10 expression is associated with shortened overall survival. Therefore, our data suggest CD10 expression may have prognostic importance in adults with de novo DLBCL.
 ...
PMID:The clinical significance of CD10 antigen expression in diffuse large B-cell lymphoma. 1193 43

Streptococcus mutans, a major etiological agent of dental caries, causes demineralization of the tooth tissue due to the formation of acids from dietary carbohydrates. Dominant among the virulence determinants of this organism are aciduricity and acidogenicity, the abilities to grow at low pH and to produce acid, respectively. The mechanisms underlying the ability of S. mutans to survive and proliferate at low pH are currently under investigation. In this study we cultured S. mutans at pH 5.2 or 7.0 and extracted soluble cellular proteins. These were analyzed using high-resolution two-dimensional gel electrophoresis, and replicate maps of proteins expressed under each of the two conditions were generated. Proteins with modulated expression at low pH, as judged by a change in the relative integrated optical density, were excised and digested with trypsin by using an in-gel protocol. Tryptic digests were analyzed using matrix-assisted laser desorption ionization mass spectrometry to generate peptide mass fingerprints, and these were used to assign putative functions according to their homology with the translated sequences in the S. mutans genomic database. Thirty individual proteins exhibited altered expression as a result of culture of S. mutans at low pH. Up-regulated proteins (n = 18) included neutral endopeptidase, phosphoglucomutase, 60-kDa chaperonin, cell division proteins, enolase, lactate dehydrogenase, fructose bisphosphate aldolase, acetoin reductase, superoxide dismutase, and lactoylglutathione lyase. Proteins down-regulated at pH 5.2 (n = 12) included protein translation elongation factors G, Tu, and Ts, DnaK, small-subunit ribosomal protein S1P, large-subunit ribosomal protein L12P, and components of both phosphoenolpyruvate:protein phosphotransferase and multiple sugar binding transport systems. The identification of proteins differentially expressed following growth at low pH provides new information regarding the mechanisms of survival and has identified new target genes for mutagenesis studies to further assess their physiological significance.
 ...
PMID:Analysis of Streptococcus mutans proteins modulated by culture under acidic conditions. 1197 12


1 2 3 4 Next >>